Simulation and Characterization of the Effects of N-linked Glycans on Glycoproteins

Many essential, highly studied proteins are glycoproteins, which contain branched chains of sugar molecules (glycans) covalently attached at specific glycosylation sites. The attributes of the glycosylation of a protein can potentially affect the protein’s structure, stability, catalytic activity, and clearance rate. Currently, there is a limited characterization of the relationship between glycosylation and the corresponding effects. This project seeks to increase the fidelity of this characterization using molecular dynamics in GROMACS of the glycoproteins Butyrylcholinesterase (BChE), a catalytic enzyme which counteracts Sarin nerve gas, and a chimeric anthrax antitoxin (CMG2-Fc). We vary the protein’s oligomerzation status and, in silico, the glycan’s composition, heterogeneity, and degree. Subsequently, we analyze the proteins structure, stability, reactivity, to draw meaningful conclusions concerning the effects of the glycans on the glycoprotein.